UCLA

Eye injuries and diseases remain as a challenging clinical issue to deal with worldwide. Due to the existence of ocular drug transport barriers, conventional administration methods have shown several limitations, such as low bioavailability and poor patient compliance. Therefore, we formulated a gelatin methacryloyl (GelMA) based nanoparticles (NPs) which can be loaded with hydrophilic drug molecules such as antibiotics. These NPs can be incorporated into a hydrogel patch composed of GelMA and low degree glycidyl methacrylated hyaluronic acid (HAGM) for sustained drug release to treat the target site of bacterial infection in the eye. The engineered GelMA based NPs were characterized in vitro and demonstrated ideal hydrodynamic size (particle diameter: 221�11 nm), homogeneity (PDI: 0.21�0.02) and loading efficiency (93.8�8.2%), facilitating drug penetration and bioavailability. The GelMA/HAGM hydrogel patch (GelPatch) was prepared by dissolving the compositions in prepolymer solution and crosslinking for 4 min under visible light (450-550 nm). The release profiles of moxifloxacin (MXF) loaded GelMA NPs incorporated inside GelPatch were studied in vitro. An initial quick release was followed by a sustained release of 70% of loaded MXF for 5 days. Such a release profile is desirable because the initial 30% of released MXF can kill bacteria and the therapeutic effect can be retained for several days. Incorporation of GelMA NPs also enhanced the mechanical properties of GelPatch, in terms of adhesion (burst pressure: 40.8�4.2 kPa), which has surpassed the eye pressure ranges (2.7-4.0 kPa) of patients with eye diseases, and elasticity (compressive modulus: 40.47�2.7 kPa, tensile modulus: 42.754�2.03 kPa). The biocompatibility of GelPatch containing NPs was confirmed in vitro by providing > 90% cell viability. The MXF loaded NPs were highly effective against both gram-positive (Pseudomonas aeruginosa) and gram-negative (Staphylococcus aureus) bacteria based on the results from zone of inhibition (diameter:28-30 mm) as well as the colony forming assay. With the advantages of easy formulation and application, good biocompatibility, and promising antibiotic functions, the GelMA NPs, together with the GelPatch, possess the potential for further application in treating many eye diseases in a safe, effective and patient compliant way.